At present, there are more than 150 millions people suffering from diabetes worldwide and it is expected that this figure will be over 300 millions by 2025. Among them, predominant are the patients suffering from type 2 diabetes (T2D). Since insulin resistance is the main metabolic abnormality of T2D, there is of considerable interest in the development of insulin-sensitizing agents, which treat diabetes by improving insulin resistance. Two major pathways have been targeted by clinical medications to ameliorate insulin resistance: peroxidsome-proliferator-activating receptors (PPARs) and AMP-activating receptors (AMPK). Thiazolidinediones (TZDs) and biguanides are the two most generally used agents for treating diabetes at present. TZDs are widely used but can result in many adverse effects, such as weight gain, fluid retention and heart failure. The dimethyl biguanide does not result in weight gain, but mainly acts in liver rather than muscles, and thus is not a satisfied therapy for treating diabetes. Therefore, there is a worldwide search for a better insulin-sensitizing agent for the treatment of diabetes.
Now, there are over one billion overweight adults. Among them, 300 millions are suffering from obesity, and this figure tends to increase quickly, resulting in a rapid increase in obesity-related diseases, such as type 2 diabetes, cardiac diseases, stroke and hypertension. The major reasons resulting in overweight and obesity are attributed to high fatty and high calorie diet, lack of exercise and the accelerating urbanization. There are only two marketed anti-obesity drugs that can be used in a long term: one is orlistat, a specific inhibitor of gastrointestinal tract lipases, but has very common gastrointestinal-related adverse effects; the other is sibutramine, a monoamine reuptake inhibitor, but it may increase blood pressure and heart rate. So there is an unmet need to develop safe and effective weight loss drugs.
Momordica charantia L. belongs to the family Cucurbitaceae and it has been widely used in China for more than 7 hundred years as a medicinal remedy for dispelling “heat”, detoxicating, improving acuity of vision, invigorating stomach, relieving thirst, stopping diarrhea and as a helminthicide. The major chemical constituents in Momordica charantia L. include triterpenoid saponins, cerebrosides and polypeptides. Although several reports in the literature have described a hypoglycemic effect of Momordica charantia L extracts, it is not known whether cucurbitane triterpenoids isolated from Momordica charantia L have similar effects to reduce hyperglycaemia. Harinantenaina et al. (Chem. Pharm. Bull 54:1017-1021, 2006) has reported that triterpene-5β, 19-epoxy-3β,25-dihydroxycucurbita-6,23(E)-diene and 3β,7β,25-trihydroxycucurbita-5,23 (E)-dien-19-al isolated from Momordica charantia L. showed hypoglycemic effect on alloxan-induced diabetic mice at a dose of 400 mg/kg but the effect they reported was very mild. Moreover, there is no report to indicate that these compounds can stimulate the glucose uptake in muscle and adipose cells, promote the translocation of the glucose transporter 4 (GLUT4) to the cell membrane, increase the activity of adenosine monophosphate activated protein kinase (AMPK) and thus can be used for prevention and treatment of diabetes and obesity.